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Technology to Enable the Clinical Genomics
Revolution
Session 100, February 13, 2019
Kate Birch, Data & Technology Program Manager, Melbourne Genomics Health
Alliance and CSIRO
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Kate Birch, BSc(Hons) MIS CHIA, has no real or apparent conflicts
of interest to report.
Conflict of Interest
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• From clinical genetics to clinical genomics
• Melbourne Genomics Health Alliance
• In clinical practice, is genomics better than standard care?
• Technology to enable genomics
• Patients views on data sharing
Agenda
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• Recognize the need for whole-of-system change in the
implementation of clinical genomics
• Demonstrate evidence for the utility and economics of genomics
as a front line test
• Distinguish the different requirements for the implementation of
technology in emerging versus established areas of clinical
practice
• Contrast the differences in data sharing preferences and concerns
between patient populations and well populations
Learning Objectives
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From genetics to genomics
• Genetics scrutinizes the functioning and composition of the
single gene where as
• Genomics addresses all genes and their inter relationships in
order to identify their combined influence on the growth and
development of the organism
World Health Organisation
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Phimister et al., NEJM 366: 757-9, 2012
Cost of sequencing a human genome
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From genetics to genomics
Integration with microbiome,
proteomics, metaboloimics...
Whole genome
Whole exome
Large panels
Small
panels
Single
gene
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From genetics to genomics
Integration with microbiome,
proteomics, metaboloimics...
Whole genome
Whole exome
Large panels
Small
panels
Single
gene
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An analogy…..
Shred them. Read each piece and reconstruct the
story. Find the typos.
Do they change the meaning of the sentence?
1000 copies
of War and
Peace = a
single
genome
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Research
Clinical care
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We know what we are doing… it will
just happen
But it typically takes 17
years!!
Half of Evidence Based
Practices ever reach
widespread clinical use
Morris
et al 2011
Slide by Dr Stephanie Best
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Only 2% of US genomic
data is used for clinical
care
Erik Jylling - Executive Vice President Health Politics at Danish Regions
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Challenges to Overcome
• Lack of evidence of effectiveness
• Lack of funding for clinical testing
• Unprepared workforce
• Concerns about ethical and legal issues
• Inadequate infrastructure
• Fragmentation and silos
• Lack of agreement about investment and priorities
Manolio et al, 2015
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Challenge:
Create whole of system
change
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Health service funding and
responsibilities
Australia’s Health 2014, AIHW
The Australian Health Care System
Complex and fragmented
Slide by Australian Genomics
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Melbourne Genomics
Health Alliance
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The Melbourne Genomic Health
Alliance set out to make Victoria a
world leader in the translation and
use of clinical genomics in
healthcare
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Targeted therapy
“Precision Medicine”
Better manage
disease risk and
preventative care
Faster diagnosis
Improved prognosis
The benefits for patients and the community
Genomic medicine in healthcare
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Approach
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Head-to-head comparison in the ‘real
world’
First line test
Right patient, right test, right time
A test of last resort
X
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In clinical practice, is
genomics better than
usual care?
Yes, often.
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Flagships: evidence to guide the use of
genomics
2014-2015
• AML
• Childhood syndromes
• Focal epilepsy
• Hereditary colorectal
cancer
• Hereditary neuropathy
2016-2018
• Complex care
• Congenital deafness
• Dilated cardiomyopathy
• Immunology
• Advanced solid cancers
• Advanced lymphoma (non-
Hodgkin)
2017-2019
• Controlling superbugs
• Bone marrow failure
• Complex neurological and
neurodegenerative
diseases
• Genetic kidney disease
• Perinatal autopsy
Right patient Right test Right
time
Right way
Acceptable Equitable
Effective
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Evaluation questions
• Clinical & cost data
• CRF and chart review
• Hospital costings
• Medicare & Pharmaceutical Benefit
Scheme
• Participant measures
• Surveys at baseline (pre-result) and post
result
• Interviews and focus groups
• Health professionals
• Participants
• Other
• Recorded consultations
• Genetic counsellor notes
Impact of test on:
• Diagnostic yield & clinical management
• Health outcomes (health system perspective)
• Family outcomes
• Policy and process
• Reanalysis of data
• Data sharing for research
• Additional (secondary) findings
• Singletons vs Trios
• Pre-test counselling
• Adoption
• How can appropriate clinician decision-
making be supported
Data collection
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Diagnostic Rate
Singleton
WES
Usual care
Stark et al.
2016
58%
14%
Childhood
Syndromes
n=80
More diagnoses than usual
14%
14%
Hereditary
Colorectal Ca.
n=35
13%
0%
Focal
Epilepsy
n=40
Perucca et al.
2017
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Experimental finding Traditional
Diagnostics
Exome
Rate of diagnosis 11% 55%
Average cost per
patient
$27,040 $6,003
Patients with improved
care outcomes
4% 16%
Melbourne Genomics study: an
Internationally-Recognised
Real-World Case-Study
“It is a game changer, both in terms of patient outcomes and economic sustainability.”
Backgroun
d
• Childhood syndromes patients (101
children).
• Royal Children’s Hospital Melbourne.
• Patients received both:
A. Traditional diagnostic tests.
B. Exome Test.
Numbers
Take-
Home
Messages
When Exome Seq was used:
• Five times more patients were
diagnosed.
• The cost per patient was reduced by
75%.
• Four times more patients had
improved care
NB. No patients required novel expensive
treatments.
Implication
s
Exomes as a diagnostic test:
• Provides spectacular diagnostic
power.
• Significantly reduces average patient
costs.
• Improves critical management care.
Five times the diagnosis at one quarter
the cost
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Most cost effective early in
patient care
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Recurrence risk 50% 25% 25% 25% <1% <1% <1% <1% <1%
Diagnosis
group
N=48
Reproductive
intervention
PGD PND PND PND PND - - - -
Recurrence risk ~10% ~10%
No diagnosis
group
N=32
Reproductive
intervention
TOP
Reproductive outcomes
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Technology to enable
clinical genomic
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Access to Genomic Information
Develop and implement a single set of standards, policies and
procedures to support a common infrastructure for the management
and use of genomic data by stakeholders in Victoria.
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Ideal end state in an unconstrained
environment
8. Clinical Tools
13. Genomic Data Repository
14. Data Integration
5. Staff to
manage the
data
People
Policy & Process
Technology
1. Standardised policy and
processes for data
management & access
(data governance)
11. Data Access Tools
12. Master
Patient Index
7. Identity & Access Management
2. Standardised
policy & processes
for patient consent
Electronic
Orders and
Results
EMR
(clinical data)
LIMS
(genomic
sequencing data)
Clinician
Knowledge
Clinical Decision Support
Tools
9. Diagnostic Tools
Curation Tools
Analysis
(Pipeline) Tools
10. Patient Tools
Education
Consent
Results
6. Staff to
manage the
technology
3. Standardised policy and
processes for test ordering
& reporting
4. Change control process
Public variant
curation data
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Traditional Software Selection
Requirements
Analysis
Software
Evaluation
Selection and
Purchase
Configuration
and
Customisation
Post-
Purchase
Business
Requirements
User
Requirements
System
Requirements
Organisational
Requirements
Commercial and
Contractual
Requirements
View to future
Requirements
?
It should definitely be black.
It should definitely be green.
Colour is unimportant.
Last week it needed to be
black, but now it absolutely
must be green.
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Diagnostic Tools Approach
Define Requirements Procure
Prototype
learnings
Future
needs
LOVD
Cpipe
SeqLine
r
EOI
Workshop
s
Pilot
Prototype
• New software
• Existing software
• Open source tool
• Supported the first
Alliance funded
tests
• What we’ve learnt we
need?
• What we can see we’ll
need soon?
• What we predict we’ll
need in the future?
• Rigorous
• In depth
• Hands on
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GenoVic
GenoVic is unique, but not new
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13. Genomic Data Repository
14. Data Integration
11. Data Access Tools
entity & Access Management
LIMS
(genomic
sequencing data)
9. Diagnostic Tools
Curation Tools
Analysis
(Pipeline) Tools
10. Patient Tools
Education
Consent
Results
Public variant
curation data
Investigation
A clinical system for genomics
Providing end-to-end modular cloud services for multiple laboratories
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Patient’s views on data
sharing
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Melbourne Genomics Health Alliance | Document Name Here41
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Executive Director Alliance members
A/Prof Clara Gaff Penny Gleason
Dr Christine Walker
Evaluation Team
Dr Melissa Martyn
Dr Emily Forbes
Anaita Kanga- Pariaba
Nessie Mupfeki
Clinical team
Elly Lynch
Genetic Counsellors
Sophie Beck
GenoVic team
Principal funder
Research by…
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Clinical consent for data sharing
• No choice: ‘Anonymised’ data is shared
• Opt in: to share re-identifiable data
98% agree
Those who did not agree
were significantly more
likely to be parents
consenting for children
p=0.001
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Survey respondents
– Administered after genetic counselling, before results received
• 87% response rate
• 31 days median time from testing consent to survey return
– Characteristics
• No significant differences to larger cohort
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Recall is high
• Vast majority of patients accurately recall their data
sharing decision
• Vast majority of patients understand anonymised data
may be shared
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Information about data sharing was
satisfactory
• Majority received enough information
• Most had no remaining concerns about data sharing
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How difficult do you think it would be for
someone to be identified from their
stored genome sequence?
&
How concerned would you be if
someone identified you from your stored
data?
Genomics Privacy
Ease of
identification
Level of concern if
identified
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Genomics Privacy
Ease of
identification
Level of concern if
identified
Easy
I am
concerned
Difficult
I am
concerned
Difficult
I’m not
worried
Easy
I’m not
worried
Patients with suspected
hereditary conditions
significantly more likely to
be concerned about being
identified
Trend towards patients
having panel testing to be
less concerned
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How broadly should data be shared?
Patient trust in sharing data
Alliance Members
Australian not-for-
profit
Overseas not-for-profit
Pharmaceutical
Government
Other Industry
High trust
Low trust
Over half said that the country
would influence their decision
I don't care about the
country as long as it was
being used in an ethical
way and for research that
would be beneficial ie not
to discriminate against
certain groups and not for
eugenics etc
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Control
Permissiveness
Ongoing use
unless opt out
Opt in each time
Opt out each time
Permanent
reuse
No permission
No clear preference for one model of
consent
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Australian Genomics Dynamic Consent
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I only want to help
cancer research. I
don’t want to …be
shared for any other
purposes
Cancer, agreed to share
I strongly believe it is
an invasion of my
privacy and sensitive
information
Hereditary, agreed to
share
No concern with..medical
professionals.
Greatly concerned if shared
more widely .e,g insurers,
employers
Cancer, agreed to share
Overall most are informed,
accepting and permissive BUT
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Melbourne Genomics – 2013-2015
CEOs/Leadership
Gareth Goodier (RMH)
Christine Kilpatrick (RCH)
Stephen Smith (University of Melbourne)
Doug Hilton (WEHI)
Kathryn North (MCRI)
Lynne Cobiac (CSIRO)
Sue Forrest (AGRF)
Steering Group
James Angus (Chair)
Julian Clark
Sue Forrest
Clara Gaff (Exec Director)
Trevor Lockett / David Hansen
Andrew Sinclair
Mike South
Paul Waring / Jon Emery
Ingrid Winship
Advisory Groups
Information Management Advisory
David Hansen (Chair)
Terry Brennan
Ken Doig
Rowan Gronlund
Andrew Lonie
Fernando Martin-Sanchez
Wayne Mather
Emeline Ramos
Brenda White
Community Advisory
Ingrid Winship (Chair)
Louisa Di Pietro
Heather Renton
Margaret Sahhar
Janney Wale
Christine Walker
Liat Watson
Clinical Interpretation
& Reporting Advisory
Paul James (Chair)
Damien Bruno
Paul Ekert
Monique Ryan
Charlotte Slade
Alison Trainer
Genomics & Bioinformatics Advisory
Graham Taylor / Alicia Oshlack (Chair)
Melanie Bahlo
Denis Bauer
Paul James
Andrew Lonie
Simon Sadedin
Kirby Siemering
Data Access Advisory
Yousef Kowsar
Kurt Lackovic
Steven Manos
Candice McGregor
Owen O’Neill
Gayle Philip
Bernie Pope
Melissa Southey
Advanced Users Group
Flagships
AML
Andrew Roberts
Ian Majewski
Seong Lin Khaw
Francoise Merchinaud
Edward Chew
CMT
Monique Ryan
Paul James
Tim Day
Lynette Kiers
Adrienne Sexton
CRC
Alex Boussioutas
Finlay Macrae
Alison Trainer
Ingrid Winship
Michael Bogwitz
CS
Sue White
Zornitza Stark
Tiong Tan
Paul Ekert
Christiane Theda
David Amor
Maie Walsh
Patrick Yap
Epilepsy
Patrick Kwan
Terry O’Brien
Ingrid Scheffer
Piero Perucca
Paul James
Laboratories
CTP
Paul Waring
Graham Taylor
Tiffany Cowie
Sebastian Lunke
Renata Marquis-Nicholson
Greg Corboy
Michael Christie
Arthur Hsu
VCGS
Graham Taylor
Damien Bruno
Steven Nasioulas
Belinda Chong
Shannon Cowie
Melanie Smith
Clare Love
Chris Guest
AGRF
Sue Forrest
Kirby Siemering
Melanie O’Keefe
Matthew Tinning
Lavinia Gordon
Rust Turakulov
Stephen Wilcox
Information Systems
CPIPE / MG LOVD VLSCI
Andrew Lonie
Simon Sadedin
John-Paul Plazzer
Charlotte Anderson
Anthony Marty
Peter Georgeson
Denis Bauer
Harriet Dashnow
Guido Grazioli
Richard Sinnott
Glenn Tesla
Clare Sloggett
Clinical Systems - MCRI & REDCAP
Jane Halliday
Susan Donath
Leanne Mills
Ross Dunn
Luke Stephens
BIOGRID
Maureen Turner
Leon Heffer
Alice Johnstone
Working Groups
Patient-entered data tool
Patient survey
Research access
Education symposium
Evaluation
Information requirements
Reporting
Database users
Pipeline platform
Project Team
Clara Gaff (Exec Director)
Tim Bakker (Info Mgmt)
Michele Cook (Admin)
Ivan Macciocca (Clinical)
Karen Meehan (Comms)
Natalie Thorne (Bioinf)
Evaluation Team
Emily Forbes
Melissa Martyn
Nessie Mupfeki
Bill Wilson
Genetic Counsellors
Gemma Brett
Emma Creed
Ella Wilkins
Health Economics
Khurshid Alam
Deborah Schofield
Rupendra Shrestha
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Melbourne Genomics – 2016-2019
Alliance Board
Catherine Walter (Chair)
Christine Kilpatrick (RMH)
Andrew Stripp (Monash Health)
Dale Fisher (PeterMac)
Christine Kilpatrick (RCH)
Shitij Kapur (UoM)
Doug Hilton (WEHI)
Kathryn North (MCRI)
Rob Grenfell (CSIRO)
Irene Kourtis (AGRF)
Sue Shilbury (Austin Health)
Anna Burgess (DHHS observer)
Executive Management Committee
Clara Gaff (Chair)
David Hansen
Andrew Sinclair
Richard King
Julian Clark
Felicity Topp
Fergus Kerr
Peter McDougall
Ingrid Winship
Sean Grimmond
Kirby Siemering
Paul Fennessy (DHHS observer)
Advisory Groups
Clinical Adoption Advisory
Fergus Kerr (Chair)
Cate Kelly
Sylvia Metcalfe
Don Campbell
Lindsay Grayson
Margaret Kelaher
Noel Cranswick
Jayesh Desai
Community Advisory
Jane Bell (Chair)
Louisa Di Pietro
Heather Renton
Margaret Sahhar
Janney Wale
Christine Walker
Liat Watson
Diagnostic Advisory
Richard King (Chair)
Kirby Siemering
Sebastian Lunke
Melanie O’Keefe
Vivien Vasic
Michael Christie
Andrew Fellowes
Suzanne Svobodova
Tony Papenfuss
Simon Sadedin
Paul James
Information Management Advisory/GenoVic
Project Control Group
David Hansen (Chair)
Wayne Mather
Rowan Gronlund
Kevin Ericksen
Tony Papenfuss
Michael Carolan
Erminia Schiavone
Kris Jenkins
Mike South
Angela Watt
Andrew Lonie
Clara Gaff
Malcolm Smart
Flagships 2016-2018
Congenital Deafness
David Amor
Lilian Downie
Valerie Sung
Libby Smith
Bibi Gerner
Matthew Hunter
Kerryn Saunders
Natasha Brown
Melissa Wake
Rachel Burt
Jane Halliday
ZeffiePoulakis
Elizabeth Rose
Complex Care in Children
Sue White
Zornitza Stark
Tiong Tan
Alison Yeung
Matthew Hunter
Katrina Harris
Dilated Cardiomyopathy
Paul James
Jay Ramchand
Matthew Wallis
David Hare
Omar Farouque
Immunology
Jo Douglass
Charlotte Slade
Vanessa Bryant
Jo Smart
Sara Barnes
Seth Masters
Mimi Tang
Ingrid Winship
Zornitza Stark
Lymphoma
Stephen Opat
Miles Prince
Gareth Gregory
Michael Dickinson
Eliza Hawkes
Piers Blombery
Solid Cancers
Jayesh Desai
Kortnye Smith
Sophie Beck
Dong Anh Khuong Quong
Hui Gan
Paul Eckert
Ben Solomon
Ben Markman
Flagships 2017-2019
Bone marrow failure
Piers Blombery
David Ritchie
Francoise Mechinaud
Anthea Greeway
Andrew Grigg
Erica Wood
Paddy Barbaro
Controlling Superbugs
Lindsay Grayson
Ben Howden
Norelle Sherry
Jason Kwong
Tony Korman
Caroline Marshall
Mark Chan
Monica Slavin
Marcel Leroi
Complex neurological
Patrick Kwan
Sam Berkovic
Martin Delatycki
Dennis Velakoulis
Michael Fahey
Melanie Bahlo
Rick Leventer
Amy Schneider
Genetic kidney disease
Catherine Quinlan
Sue White
Zornitza Stark
Ella Wilkins
Mathew Wallis
David Power
Kathy Nicholls
Peter Kerr
Perinatal autopsy
George McGillivray
Jacqueline Collett
Ian Simpson
Trishe Leong
Jan Pyman
Alison Yeung
Natasha Brown
Sue White
Sue Walker
Laboratories
CTP
Paul Waring
Graham Taylor
Tiffany Cowie
Sebastian Lunke
Renata Marquis-Nicholson
Greg Corboy
Michael Christie
Arthur Hsu
VCGS
Graham Taylor
Damien Bruno
Steven Nasioulas
Belinda Chong
Shannon Cowie
Melanie Smith
Clare Love
Chris Guest
AGRF
Sue Forrest
Kirby Siemering
Melanie O’Keefe
Matthew Tinning
Lavinia Gordon
Rust Turakulov
Stephen Wilcox
Information Systems
CPIPE / MG LOVD VLSCI
Andrew Lonie
Simon Sadedin
John-Paul Plazzer
Charlotte Anderson
Anthony Marty
Peter Georgeson
Michael Milton
Juny Kesumadewi
Gayle Philips
Denis Bauer
Harriet Dashnow
Guido Grazioli
Richard Sinnott
Glenn Tesla
Clare Sloggett
Clinical Systems - MCRI & REDCAP
Jane Halliday
Susan Donath
Leanne Mills
Ross Dunn
Luke Stephens
BIOGRID
Maureen Turner
Leon Heffer
Alice Johnstone
Working Groups
Patient-entered data tool
Patient survey
Research access
Education symposium
Evaluation
Information requirements
Reporting
Database users
Pipeline platform
Curation tool pilot evaluators
Curation tool RFQ evaluators
Analysis tool user group
Curation tool user group
Information architecture reference group
Genetic Counsellors
Gemma Brett
Emma Creed
Anna Jarmolowicz
Ivan Macciocca
Ellie Prawer
Giulia Valente
Kirsty West
Health Economics
Khurshid Alam
Deborah Schofield
Rupendra Shrestha
Melbourne Genomics Health Alliance Program
Team
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